Compositions with reactive ingredients, and wound dressings, apparatuses, and methods

ABSTRACT

Wound dressings and wound inserts comprising substantially dry reactive agents, methods of forming wound inserts comprising dry reactive agents, and wound-treatment methods.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 61/323,663, filed Apr. 13, 2010, which is incorporated herein in itsentirety.

BACKGROUND

1. Field of the Invention

The present invention relates generally to healing of wounds andwound-treatment therapies. More particularly, but not by way oflimitation, the present invention relates to fluid-instillation andnegative-pressure wound therapies, comprising a foam (and/or otherporous material) wound insert containing reactive agents.

2. Background Information

Clinical studies and practice have shown that providing a reducedpressure in proximity to a tissue site augments and accelerates thegrowth of new tissue at the tissue site. The applications of thisphenomenon are numerous, but application of reduced pressure has beenparticularly successful in treating wounds. This treatment (frequentlyreferred to in the medical community as “negative pressure woundtherapy,” “reduced pressure therapy,” or “vacuum therapy”) provides anumber of benefits, including faster healing and increased formulationof granulation tissue. Typically, reduced pressure is applied to tissuethrough a wound insert (e.g., a porous pad or other manifold device).The wound insert typically contains cells or pores that are capable ofdistributing reduced pressure to the tissue and channeling fluids thatare drawn from the tissue. The wound insert can be incorporated into awound dressing having other components that facilitate treatment, suchas, for example, a drape (e.g., adhesive surgical drape). Instillationof fluids (e.g., irrigation fluids and/or medicaments) may be used inconjunction with negative pressure wound therapy to promote healingand/or improve efficacy. One example of a system for delivering activesolutions to a wound is disclosed in U.S. Pat. No. 6,398,767.

SUMMARY

The present disclosure includes embodiments of wound inserts, wounddressings, methods of forming wound inserts, and wound-treatmentmethods.

Some embodiments of the present wound inserts are for use between awound of a patient and a drape coupled to skin around the wound suchthat the drape covers the wound and forms a space between the drape andthe wound. Some embodiments of the present wound inserts comprise: anopen-celled foam (e.g., configured to be disposed between a wound of apatient and a drape coupled to skin adjacent the wound, e.g., such thatthe drape forms a space between the wound and the drape); and a reactiveagent disposed within the foam, and configured to be inert in theabsence of an activating fluid and to exhibit antimicrobial propertieswhen released by an activating fluid.

In some embodiments, the reactive agent is configured to react withwater (and/or aqueous solution) to release hypochlorite ion and/or formhypochlorous acid, depending on In some embodiments, the reactive agentcomprises a hypochlorite salt. In some embodiments, the reactive agentcomprises a substance defined by M(OCl)n, where n=1 if M is K⁺, Li⁺, orNa⁺, and where n=2 if M is Ca²⁺ or Mg²⁺. In some embodiments, thereactive agent comprises at least one of: an N-chloro taurine; anN,N-dichloro taurine; an N-halogenated amino acid; an N,N-dihalogenatedamino acid; or a combination of any two or more of these. Someembodiments comprise (alternatively or additionally) an agent comprisinga growth factor; a protein; a peptide; or a combination thereof.

In some embodiments, the wound insert comprises a suspension agentincluding at least one of: a polyvinylpyrrolidone, a polyethylene oxide,a polyvinyl acetate (PVA), a polyvinyl alcohol (PVOH), an ethylene vinylalcohol (EVOH) copolymer, an ethylene styrene copolymer,polycaprolactone (PCL), polysorbate, or a combination of any two or moreof these. In some embodiments, the suspension agent couples the reactiveagent to the foam. In some embodiments, the suspension agentencapsulates the reactive agent. In some embodiments, the suspensionagent is configured to dissolve in the presence of a solvent. In someembodiments, the suspension agent is water soluble. In some embodiments,the wound insert is configured to release a hypochlorite ion in thepresence of a volume of activating liquid such that after release thevolume of activating liquid will have a concentration of hypochloriteion between 0.7 and 20 millimolar. In some embodiments, the wound insertis configured to release a hypochlorite ion in the presence of each ofthree or more sequential volumes of activating liquid such that afterrelease each sequential volume of activating liquid will have aconcentration of hypochlorite ion between 0.7 and 20 millimolar.

In some embodiments, the reactive agent is dispersed throughout at leasta portion of the foam. In some embodiments, the foam comprises siliconepolymer. In some embodiments, the foam comprises a fluoropolymer. Insome embodiments, the fluoropolymer comprises at least one of:polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF),perfluoroalkoxy (PFA) polymer, fluoroethylkene (FEP), or a combinationof any two or more of these. In some embodiments, the foam comprises atleast one of a polyolefin or polyolefin copolymer. In some embodiments,the polyolefin includes at least one of: polyethylene (PE),polypropylene (PP), polybutylene (PB), ethylene-vinyl acetate (EVA),copolymers of any of these or a combination of any two of these.

Some embodiments further comprise: a second open-celled foam that is notcoupled to the reactive agent; where the first open-celled foam isconfigured to be inert in the present of the reactive agent, and forms afirst layer of the wound insert; and where the second open-celled foamforms a second layer of the wound insert, and is coupled to the firstopen-celled foam.

Some embodiments of the present wound inserts comprise: an open-celledfoam configured to be disposed between a wound of a patient and a drapecoupled to skin adjacent the wound (e.g., such that the drape forms aspace between the wound and the drape), the foam having an upper sideand lower side configured to face the wound; a plurality of particles ofa first metal dispersed within the foam; and a second metal coupled tothe lower side of the foam, and configured such that a fluid can beintroduced to generate microcurrents between the first metal and thesecond metal. In some embodiments, the first metal is dispersed in thefoam such that if a fluid passes through the foam at least some portionof the first metal will exit the foam.

Some embodiments further comprise: a permeable layer coupled to thelower side of the foam; where the second metal is coupled to thepermeable layer. In some embodiments, the wound insert is configuredsuch that if a fluid is passed through the foam from the upper sidethrough the lower side, at least some portion of the first metal willexit the foam through the lower side and pass through the permeablelayer. In some embodiments, the wound insert is configured such that ifthe wound insert is disposed such that the permeable layer is in contactwith a wound and a fluid is passed through the foam from the upper sideto the lower side, at least some portion of the first metal will exitthe foam through the permeable layer and microcurrents will be generatedbetween the first metal and the second metal coupled to the permeablelayer. In some embodiments, the first metal comprises silver. In someembodiments, the second metal comprises zinc.

In some embodiments, the present wound inserts are in combination with adrape configured to be coupled to skin adjacent a wound of a patient. Insome embodiments, the present wound inserts are in combination with afluid delivery pad configured to be coupled to the drape and a fluidsource such that the fluid source is actuatable to deliver a fluid to awound through the wound dressing. In some embodiments, the present woundinserts are in combination with a fluid source configured to be coupledto the wound dressing such that the fluid source is actuatable todeliver a fluid to the wound dressing. In some embodiments, the presentwound inserts are in combination with a vacuum source configured to becoupled to the wound dressing such that the vacuum source is actuatableto apply negative pressure to the wound dressing.

Some embodiments of the present wound dressings comprise: one or more ofany of the present wound inserts; and a drape configured to be coupledto skin adjacent a wound of a patient (e.g., such that the drape coversthe wound insert and forms a space between the wound and the drape).Some embodiments further comprise: a fluid delivery pad configured to becoupled to the drape and a fluid source such that the fluid source isactuatable to deliver a fluid to a wound through the wound dressing.

Some embodiments of the present wound-treatment apparatuses comprise: awound dressing with a drape and one or more of any of the present woundinserts; and a fluid source configured to be coupled to the wounddressing such that the fluid source is actuatable to deliver a fluid tothe wound dressing. Some embodiments further comprise: a vacuum sourceconfigured to be coupled to the wound dressing such that the vacuumsource is actuatable to apply negative pressure to the wound dressing.

Some embodiments of the present methods comprise: adding (e.g., dry)hypochlorite salt particles to a solution such that the solution andhypochlorite salt form a slurry, the solution comprising a polymer and aliquid that is a solvent of the polymer but not a solvent of thehypochlorite salt; and substantially removing the liquid from the slurrysuch that at least a portion of the hypochlorite salt particles are atleast partially encapsulated by the polymer. In some embodiments, thehypochlorite salt is defined by M(OCl)n, where n=1 if M is K⁺, Li⁺, orNa⁺, and where n=2 if M is Ca²⁺ or Mg²⁺. In some embodiments, thehypochlorite salt is defined by Ca(OCl)₂. In some embodiments, thepolymer is biocompatible and optionally biodegradable. In someembodiments, the polymer is not water soluble. In some embodiments, thepolymer comprises polycaprolactone (PCL). In some embodiments, thesolvent is non-aqueous. In some embodiments, the solvent comprises atleast one of Dichloromethane (DCM or methylene chloride),Tetrahydrofuran (THF), or Cyclohexane. Some embodiments furthercomprise: disposing, prior to substantially removing the liquid, a foamin the slurry such that hypochlorite salt particles and polymer aredispersed within the foam. Some embodiments further comprise: reducing,prior to adding the hypochlorite salt particles into the solution, thesize of the hypochlorite salt particles such that a majority of thehypochlorite salt particles have a size at or below a target size. Insome embodiments, the target size is 180 microns.

Some embodiments of the present methods of forming a wound insertcomprise: applying negative pressure to an open-celled foam to drawparticles into the foam such that the particles become dispersedthroughout at least a portion of the foam. In some embodiments, the foamhas a first side and a second side opposite the first side, and themethod further comprises: disposing the foam between a filter configuredand a particle reservoir such that the filter is adjacent the first sideof the foam and the reservoir is adjacent the second side, the filterconfigured to substantially prevent passage of the particles through thefilter; and where applying negative pressure comprises applying negativepressure to the filter such that the particles are drawn from thereservoir into the foam.

In some embodiments, the particles comprise a reactive agent. In someembodiments, the reactive agent is configured to react with water (andor aqueous solution) to release hypochlorite ion and/or formhypochlorous acid, depending on pH. In some embodiments, the reactiveagent comprises hypochlorite. In some embodiments, the reactive agentcomprises a substance defined by M(OCl)n, where n=1 if M is K⁺, Li⁺, orNa⁺, and where n=2 if M is Ca²⁺ or Mg²⁺. In some embodiments, thereactive agent comprises at least one of: an N-chloro taurine; anN,N-dichloro taurine; an N-halogenated amino acid; an N,N-dihalogenatedamino acid; or a combination of any two or more of these. Someembodiments comprise (alternatively or additionally) an agent comprisinga growth factor; a protein; a peptide; or a combination thereof. In someembodiments, the particles comprise a metal. In some embodiments, theparticles comprise silver.

In some embodiments, the particles comprise a suspension agent includingat least one of: a polyvinylpyrrolidone, a polyethylene oxide, apolyvinyl acetate (PVA), a polyvinyl alcohol (PVOH), an ethylene vinylalcohol (EVOH) copolymer, an ethylene styrene copolymer,polycaprolactone (PCL), polysorbate, or a combination of any two or moreof these. In some embodiments, the suspension agent is configured tobind the reactive agent to the foam. In some embodiments, the suspensionagent encapsulates the reactive agent. In some embodiments, thesuspension agent is configured to dissolve in the presence of a solvent.In some embodiments, the suspension agent is water soluble.

In some embodiments, the foam comprises silicone polymer. In someembodiments, the foam comprises a fluoropolymer. In some embodiments,the fluoropolymer comprises at least one of: polytetrafluoroethylene(PTFE), polyvinylidene fluoride (PVDF), perfluoroalkoxy (PFA) polymer,fluoroethylkene (FEP), or a combination of any two or more of these. Insome embodiments, the foam comprises at least one of a polyolefin orpolyolefin copolymer. In some embodiments, the polyolefin includes atleast one of: polyethylene (PE), polypropylene (PP), polybutylene (PB),ethylene-vinyl acetate (EVA), copolymers of any of these, or acombination of any two of these.

Some embodiments of the present wound-treatment methods comprise:delivering a fluid to a wound through a wound dressing comprising: adrape coupled to skin adjacent a wound of a patient (e.g., such that thedrape covers the wound and forms a space between the drape and thewound); an open-celled foam wound insert disposed between the drape andthe wound (e.g., in the space); and a reactive agent dispersedthroughout at least a portion of the wound inserts such that upondelivery of the fluid to the wound insert the fluid causes at least aportion of the reactive agent to pass from the wound insert to thewound. In some embodiments, delivering a fluid comprises activating afluid source that is coupled to the wound dressing to deliver the fluidto the wound through the wound dressing. Some embodiments furthercomprise: applying negative pressure to the wound through the wounddressing. In some embodiments, applying negative pressure comprisesactivating a vacuum source that is coupled to the wound dressing toapply the vacuum to the wound through the wound dressing.

Some embodiments of the present wound-treatment methods comprise:delivering a fluid to a wound through a wound dressing comprising: adrape coupled to skin adjacent a wound of a patient (e.g., such that thedrape covers the wound and forms a space between the drape and thewound); an open-celled foam wound insert disposed between the drape andthe wound (e.g., in the space); and a plurality of particles of a firstmetal dispersed within the foam; a second metal coupled to the lowerside of the foam, and configured such that upon delivery of the fluidmicrocurrents are generated between the first metal and the secondmetal. In some embodiments, the first metal is dispersed in the foamsuch that when the fluid is delivered it passes through the foam and atleast some portion of the first metal exits the foam.

In some embodiments, the wound dressing further comprises: a permeablelayer coupled to a lower side of the wound insert; and where the secondmetal is coupled to the permeable layer. In some embodiments, the wounddressing is configured such that upon delivery of the fluid to the wounddressing the fluid passes through the wound insert from an upper sidethrough the lower side, and at least some portion of the first metalexits the foam through the lower side and passes through the permeablelayer. In some embodiments, the wound insert is disposed such that thepermeable layer is in contact with the wound such that upon delivery ofthe fluid to the wound dressing the fluid passes through the foam fromthe upper side to the lower side, at least some portion of the firstmetal exits the foam through the permeable layer and microcurrents aregenerated between the first metal and the second metal coupled to thepermeable layer. In some embodiments, the first metal comprises silver.In some embodiments, the second metal comprises zinc.

Some embodiments of the present wound inserts comprise: an open-celledand/or hydrophilic foam configured to be disposed between a wound of apatient and a drape coupled to skin adjacent the wound (e.g., such thatthe drape forms a space between the wound and the drape); and a liquidsolution comprising an antimicrobial agent, the liquid solution disposedwithin the foam. In some embodiments, the foam comprises a PVOH foam. Insome embodiments, the antimicrobial agent comprises polyhexanide. Someembodiments comprise a container enclosing the foam and configured toprevent evaporation of the liquid solution. In some embodiments, thecontainer comprises a foil pouch. In some embodiments, the containercomprises a plastic pouch.

Some of the present embodiments include an open-celled foam wound insertcomprising a reactive agent disposed within the wound insert, andconfigured to be inert in the absence of an activating fluid and toexhibit antimicrobial properties in the presence of an activating fluid,for use in a wound treatment method comprising the step of delivering afluid to a wound through a wound dressing comprising: a drape coupled toskin adjacent a wound of a patient such that the drape covers the woundand forms a space between the drape and the wound; the insert disposedin the space; and where the wound insert is configured such that whenthe fluid is delivered to the wound insert, at least a portion of thereactive agent passes from the wound insert to the wound. Suchembodiments may optionally include any features described herein inrelation to other embodiments, such as, for example, the featuresdescribed in relation to methods of treatment.

Some of the present embodiments include a reactive agent configured tobe inert in the absence of an activating fluid and to exhibitantimicrobial properties in the presence of an activating fluid, for usein a wound treatment method comprising the step of delivering a fluid toa wound through a wound dressing comprising: a drape coupled to skinadjacent a wound of a patient such that the drape covers the wound andforms a space between the drape and the wound; the insert disposed inthe space; and the reactive agent disposed within the wound insert, andconfigured to be inert in the absence of an activating fluid and toexhibit antimicrobial properties in the presence of an activating fluid;where the wound insert is configured such that when the fluid isdelivered to the wound insert, at least a portion of the reactive agentpasses from the wound insert to the wound. Such embodiments mayoptionally include any features described herein in relation to otherembodiments, such as, for example, those features described in relationto methods of treatment.

Any embodiment of any of the present systems and/or methods can consistof or consist essentially of—rather thancomprise/include/contain/have—any of the described steps, elements,and/or features. Thus, in any of the claims, the term “consisting of” or“consisting essentially of” can be substituted for any of the open-endedlinking verbs recited above, in order to change the scope of a givenclaim from what it would otherwise be using the open-ended linking verb.

Details associated with the embodiments described above and others arepresented below.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings illustrate by way of example and not limitation.For the sake of brevity and clarity, every feature of a given structureis not always labeled in every figure in which that structure appears.Identical reference numbers do not necessarily indicate an identicalstructure. Rather, the same reference number may be used to indicate asimilar feature or a feature with similar functionality, as maynon-identical reference numbers.

FIG. 1 depicts a side view of one of the present wound dressings havingone of the present wound inserts and coupled to a wound site and to awound treatment apparatus.

FIG. 2 depicts an enlarged side view of the wound insert of FIG. 1.

FIG. 3A depicts a schematic block diagram of one embodiment of a woundtreatment apparatus that can comprise and/or be coupled to and/or beused with the present wound dressings and/or wound inserts.

FIG. 3B depicts an enlarged cross-sectional view of one of the presentwound dressings coupled to a wound.

FIG. 4 depicts a photograph of a silicone foam suitable for someembodiments of the present wound inserts.

FIG. 5 depicts a photograph of a silicone foam deposited with Ca(OCl)₂salt.

FIGS. 6A-6C illustrate certain characteristics of various components ofthe present wound inserts.

FIG. 7 depicts release profiles of silicone foam deposited with NaOClsalt.

FIG. 8 depicts a release profile of silicone foam deposited withPEO/NaOCl.

FIG. 9 depicts a release profile of silicone foam deposited withPCL/Ca(OCl)₂.

FIG. 10 depicts a release profile of foam deposited with Luvitec®K90/NaOCl.

FIG. 11 depicts a release profile of foam deposited with PSES/NaOCl.

FIGS. 12A and 12B depict charts of stability data for hypochlorous acidsolutions in various foams.

FIGS. 13A-13E depict photographs illustrating tests performed on variousfoams to determine stability of the foams in contact with hypochlorousacid solution.

FIG. 14 depicts a chart of hypochlorite concentration (at various times)over multiple cycles of instilling saline solution through one of thepresent wound inserts at two different hold times for each cycle.

FIG. 15 depicts a flowchart of one of the present methods.

FIG. 16 depicts a housing suitable for use in certain embodiments of thepresent methods.

FIG. 17 depicts a chart of hypochlorite concentration for two differentconcentrations of calcium hypochlorite in a wound insert over multiplesequential cycles.

FIG. 18 depicts an alternate embodiment of one of the present woundinserts.

FIG. 19 depicts a cross-sectional side view of an apparatus for makingsome embodiments of the present wound inserts.

FIG. 20 depicts an exploded perspective view of another embodiment ofthe present wound inserts.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The term “coupled” is defined as connected, although not necessarilydirectly, and not necessarily mechanically; two items that are “coupled”may be integral with each other. The terms “a” and “an” are defined asone or more unless this disclosure explicitly requires otherwise. Theterms “substantially,” “approximately,” and “about” are defined aslargely but not necessarily wholly what is specified, as understood by aperson of ordinary skill in the art.

The terms “comprise” (and any form of comprise, such as “comprises” and“comprising”), “have” (and any form of have, such as “has” and“having”), “include” (and any form of include, such as “includes” and“including”) and “contain” (and any form of contain, such as “contains”and “containing”) are open-ended linking verbs. As a result, awound-treatment method that “comprises,” “has,” “includes” or “contains”one or more steps possesses those one or more steps, but is not limitedto possessing only those one or more steps. Likewise, a wound dressingthat “comprises,” “has,” “includes” or “contains” one or more elementspossesses those one or more elements, but is not limited to possessingonly those elements. For example, in a wound dressing that comprises oneof the present wound inserts and a drape, the wound dressing includesthe specified elements but is not limited to having only those elements.For example, such a wound dressing could also include a connection padconfigured to be coupled to a negative pressure wound therapy (NPWT)apparatus (e.g., including a vacuum source and/or a fluid source).

Further, a device or structure that is configured in a certain way isconfigured in at least that way, but it may also be possible for it tobe configured in other ways than those specifically described.

Referring now to the drawings, and more particularly to FIG. 1, showntherein is an embodiment of one of the present wound treatment system10. In the embodiment shown, apparatus 10 comprises a wound-treatmentapparatus 14, and a wound dressing 18. In the embodiment shown,apparatus 14 is coupled to wound dressing 18 by a conduit 22. As shown,dressing 18 is configured to be coupled to (and is shown coupled to) awound 26 of a patient 30. More particularly, in the embodiment shown,dressing 18 comprises a wound insert 34 and a drape 38. As shown, woundinsert 34 is configured to be positioned (and is shown positioned) onwound 26 (e.g., on or adjacent to wound surface 42), and drape 38 isconfigured to be coupled to (and is shown coupled to) skin 46 of thepatient adjacent to wound 26 such that drape 38 covers wound insert 34and wound 26 (e.g., such that drape 38 forms a space 50 between drape 38and wound 26 (e.g., wound surface 42)).

Apparatus 14 can comprise, for example, a vacuum source configured to beactuatable (and/or actuated) to apply negative pressure (e.g., viaconduit 22) to wound dressing 18, a fluid source configured to beactuatable (and/or actuated) to deliver (e.g., via conduit 22) a fluid(e.g., and instillation fluid such as a medicinal fluid, antibacterialfluid, irrigation fluid, and or the like) to wound dressing 18. System10 can be implemented and/or actuated and/or coupled to patient 30 inany of various configurations and/or methods described in thisdisclosure. Additionally, various wound therapy systems and componentsare commercially available through and/or from KCI USA, Inc. of SanAntonio, Tex., U.S.A.

Conduit 22 can comprise a single lumen conduit (e.g., switched between avacuum source and/or a fluid source and apparatus 14), or can comprisemultiple single-lumen conduits or a multi-lumen conduit such that, forexample, fluid can be delivered and/or negative pressure can be appliedto wound dressing 18 individually and/or simultaneously. Additionally,conduit 22 can comprise, for example, a first lumen for the applicationof negative pressure and/or fluid delivery, and at least one additionallumen for coupling to pressure sensor(s) to sense pressure or negativepressure between drape 38 and surface 42. In some embodiments, conduit22 can comprise multiple lumens (e.g., as in a single conduit with acentral lumen for application of negative pressure and/or fluiddelivery, and one or more peripheral lumens disposed adjacent or aroundthe central lumen such that the peripheral lumens can be coupled to apressure sensor to sense a pressure or negative pressure between drape38 and surface 42 (e.g. in space 50). The lumens may be arranged with acentral lumen and other lumens disposed radially around the centrallumen, or in other suitable arrangements. The lumens may also beprovided in separate conduits. In the embodiment shown, system 10further comprises a wound dressing connection pad 54 configured to becoupled (and is shown coupled) to conduit 22. One example of a suitableconnection pad 54 is the “V.A.C. T.R.A.C.® Pad,” commercially availablefrom KCI. One example of a suitable drape 38 includes the “V.A.C.®Drape” commercially available from KCI. Another example of a connectionpad 54 is disclosed in U.S. patent application Ser. No. 11/702,822,incorporated above.

Referring now to FIG. 2, a side view of a wound insert 34 is shown.Wound insert 34 has an upper side 100, a lower side 104, lateral sides108, 112 and interior volume 116. Although one side is shown of woundinsert 34, it will be understood by those of ordinary skill in the artto wound insert 34 includes a three-dimensional, rectangular volume(shown with rectangular faces) having a depth extending perpendicular tothe side shown. In other embodiments, wound insert 34 can have asuitable shape, such as, for example, a round cylindrical shape, afanciful shape, or may be trimmed to fit an irregular shape of a wound(e.g., 26 and/or wound surface 42). Wound insert 34 may comprise a foam,such as, for example, an open-celled (and/or reticulated) foam.

Embodiments of the present wound treatment methods may be betterunderstood with reference to FIG. 3, which depicts a schematic blockdiagram of one embodiment of system 10. In the embodiment shown, wounddressing 18 is coupled to apparatus 14, and apparatus 14 comprises avacuum source 200 (e.g., a vacuum pump and/or the like) coupled to acanister 204 (e.g., configured to receive exudate and/or the like fromwound dressing 18) by way of a conduit 208. In the embodiment shown,apparatus 14 further comprises: a pressure sensor 212 having a firstpressure transducer 216 coupled to conduit 208 by way of conduit 220and/or tee-fitting 224, and a second pressure transducer 228 coupled tocanister 204 and/or wound dressing 18 by way of conduit 232. In this waypressure sensor 212 can sense and/or detect the negative pressure inwound dressing 18 and/or any of the various conduits coupled wounddressing 18, pressure sensor 212, and/or vacuum source 200.

In the embodiment shown, apparatus 14 further comprises a pressurerelease valve 236 coupled to conduit 232. Further, in the embodimentshown, canister 204 and vacuum source 200 are coupled to wound dressing18 by way of conduit 240. In the embodiment shown canister 204 cancomprise a filter 244 at or near an outlet of canister 204 to preventliquid or solid particles from entering conduit 208. Filter 244 cancomprise, for example, a bacterial filter that is hydrophobic and/orlipophilic such that aqueous and/or oily liquids will bead on thesurface of the filter. Apparatus 14 is typically configured such thatduring operation vacuum source 200 will provide sufficient airflowthrough filter 244 that the pressure drop across filter 244 is notsubstantial (e.g., such that the pressure drop will not substantiallyinterfere with the application of negative pressure to wound dressing 18from vacuum source 200).

In the embodiment shown, apparatus 14 further comprises a fluid source248 coupled to wound dressing 18 by way of a conduit 252 that is coupledto conduit 240 such as, for example, by way of a tee- or other suitablefitting 256. In some embodiments, tee fitting 256 can comprise a switchvalve and with like such that communication can be selectively permittedbetween wound dressing 18 and vacuum source 200, or between wounddressing 18 and fluid source 248. In some embodiments apparatus 14comprises only one of vacuum source 200 and fluid source 248. Inembodiments of apparatus 14 that comprise only fluid source 248,canister 204 and/or pressure sensor 212 can also be omitted. Variousembodiments, such as the one shown, conduit 232 and/or conduit 240and/or conduit 252 can be combined and/or comprised in a singlemulti-lumen conduit, such as is described above with reference toFIG. 1. In various embodiments, such as the one shown in FIG. 3A,apparatus 14 can be configured such that as soon as the liquid in thecanister reaches a level where filter 244 is occluded, a much-increasednegative (or subatmospheric) pressure occurs in conduit 208 and isdetected by transducer 216. Transducer 216 can be connected to circuitrythat interprets such a pressure change as a filled canister and signalsthis by means of a message on an LCD and/or buzzer that canister 204requires emptying and/or replacement, and/or that automatically shutsoff or disables vacuum source 200.

Apparatus 14 can also be configured to apply intermittent negative (orsubatmospheric) pressure to the wound site, and/or such that pressurerelief valve 236 enables pressure at the wound site to be brought toatmospheric pressure rapidly. Thus, if apparatus 14 is programmed, forexample, to relieve pressure at ten-minute intervals, at these intervalspressure relief valve 236 can open for a specified period, allow thepressure to equalize at the wound site (to allow pressure at the woundsite to equalize with atmospheric pressure), and then close to restorethe negative pressure (allow the pump to restore negative pressure atthe wound site). It will be appreciated that when constant negativepressure is being applied to the wound site, valve 236 remains closed toprevent leakage to or from the atmosphere. In this state, it is possibleto maintain negative pressure at the wound site without running and/oroperating pump 200 continuously, but only from time to time orperiodically, to maintain a desired level of negative pressure (i.e. adesired pressure below atmospheric pressure), which is detected bytransducer 216. This saves power and enables the appliance to operatefor long periods on its battery power supply.

FIG. 3B depicts an enlarged cross-sectional view of one of the presentwound dressings 18 coupled to wound 26. In FIG. 3B, wound 26 isillustrated as an infected wound having a plurality of microorganisms 28(e.g., bacteria) or biofilm infecting wound surface 42 and/or a depth oftissue beneath wound surface 42. More particularly, and as describedabove for FIG. 1, wound dressing 18 comprises wound insert 34 disposedadjacent or on wound 26 (e.g., wound surface 42), and drape 38 coupledto skin 46 adjacent wound 26 such that drape 38 covers wound insert 34and wound 26 and forms a space 50 between wound surface 42 and drape 38.In the embodiment shown, a first connection pad 54 a is coupled to drape38 and configured to be coupled to a fluid source (e.g., 248) by a fluidconduit (e.g., 252) such that the fluid source can be activated todeliver a fluid (e.g., saline) to wound 26 (e.g., wound surface 42)through wound dressing 18; and a second connection pad 54 b is coupledto drape 38 and configured to be coupled to a vacuum source (e.g., 200)by a conduit (e.g., 240) such that the vacuum source can be activated toapply negative pressure to wound 26 (e.g., wound surface 42) throughwound dressing 18. Wound insert 34 comprises an open-celled foam that isconfigured to be (and is shown) disposed between wound 26 and drape 38.Additionally, in the embodiment shown, wound insert 34 comprises areactive agent deposited on or in (e.g., dispersed throughout at least aportion of) wound insert 34 such that upon delivery of a fluid to woundinsert 34 the fluid reacts with and/or causes at least a portion of thereactive agent to pass from wound insert 34 to wound 26.

Some embodiments of the present methods can also be understood withreference to FIGS. 3A and 3B. For example, some embodiments of thepresent wound-treatment methods comprise delivering a fluid to a wound(e.g., 26) through a wound dressing (e.g., 18) comprising a wound insertcomprising a reactive agent deposited on or in the wound dressing suchthat the fluid reacts with and/or causes at least a portion of thereactive agent to pass from the wound insert to the wound. In someembodiments, delivering a fluid comprises activating a fluid source(e.g., 248) that is coupled to the wound dressing to deliver the fluidto the wound through the wound dressing. Some embodiments furthercomprise applying negative pressure (e.g., after and/or simultaneouslywith delivering a fluid) to the wound through the wound dressing. Insome embodiments, applying negative pressure comprises activating avacuum source (e.g., 200) that is coupled to the wound dressing to applythe negative pressure to the wound through the wound dressing. Arrows inFIG. 3B indicate the flow of fluid (and reactive agent and/or a productof the reactive agent and the fluid) to and from wound surface 42 (e.g.,through wound insert 34) such that the reactive agent (and/or a productof the reactive agent and the fluid) can kill microorganisms 28 toreduce and/or eliminate infection of wound 26.

Hypochlorous acid (HOCl) and hypochlorite ion (ClO—, which is alsocommonly referred to, generally understood to be synonymous with, andmay be referred to interchangeably in this disclosure as, OCl—) areexamples of effective antimicrobial agents for biocidal action. Forexample, HOCl is typically capable of killing a broad spectrum ofmicrobes (e.g., fungus, bacteria, viruses, fungus, yeast, and the like);often in a relatively short period of time (e.g., is capable of killinggreater than 99% of microbes within a period of less than 10 seconds).Such antimicrobial agents can be generated or formed by a combination ofthe present reactive agents and fluid (e.g., water and/or aqueoussolution, such as, for example, saline solution) and may be moreeffective and/or more versatile than antibiotics and other commonly usedantimicrobial agents used in wound treatment in the past. For example,antibiotics may be bacteria-specific such that testing may be requiredto determine a suitable antibiotic to use for a specific wound orinfection; and/or such that antibiotics may have only limitedeffectiveness for individual wounds and/or infections (e.g., wheretesting is not performed and/or where a wound is infected with aplurality of different bacteria). Such testing may take as long asseveral days to determine an appropriate antibiotic, delaying treatmentor selection of an effective antibiotic. Additionally, bacteria maydevelop resistance to antibiotics, such that antibiotics may havereduced effectiveness after an amount of time. Further, antibiotics aretypically administered intravenously (systemically) such thatantibiotics may kill beneficial bacteria (e.g., in a patient's digestivesystem) and/or may cause organ damage (e.g., to a patient's liver).

Experiments were performed for some of the present reactive agents(and/or resulting solutions) to investigate their antibacterialproperties. In a first experiment, an even monolayer ofMethicillin-resistant Staphylococcus aureus (MRSA) bacteria was spreadacross the surface of each of several petri dishes, and either a 30 μgcontrol dose of Vancomycin, or an 8 mm×5 mm piece of sponge was placedon each petri dish. The pieces of sponge included: a piece ofpolyurethane foam coated with a silver (Ag), a piece of dry siliconefoam, a piece of silicone foam impregnated with a Polyhexanide solution,a piece of silicone foam deposited with Ca(ClO)₂ salt, and a piece ofsilicone foam deposited with NaClO salt. After placement of the piecesof foam, saline was dropped onto the foams deposited with Ca(ClO)₂ andNaClO salts, respectively, Each petri dish was incubated for eighteen(18) hours at 37° C., and the clear area in which the bacteria had beenkilled (inhibition zone) was measured. The foam with NaClO resulted inan inhibition zone of approximately 1600 mm², and the foam with Ca(ClO)₂resulted in an inhibition zone of approximately 800 mm². Thenext-closest was the one 30 μg control dose of Vancomycin, whichresulted in an inhibition zone of 200 mm². In a second, similarexperiment, the monolayer of bacteria was E. Coli instead of MRSA, andthe remainder of the second experiment was substantially the same as thefirst. The results of the second experiment were also similar. The foamwith NaClO resulted in an inhibition zone of approximately 1050 mm², andthe foam with Ca(ClO)₂ resulted in an inhibition zone of approximately800 mm². The next-closest was the polyurethane foam with silver, whichresulted in an inhibition zone of approximately 100 mm². From thesepreliminary experiments, the inventors believe the present reactiveagents and the resulting solutions to have effective antimicrobialproperties. The reactive agents (and/or antimocrobial products of thereactive agents) of the present embodiments can be configured to have abroad-spectrum killing power that will kill a variety of microbes (e.g.,fungus, bacteria, viruses, fungus, yeast, etc.). Additionally, thepresent reactive agents (and/or antimocrobial products of the reactiveagents) can be delivered locally (preventing systemic damage or otherside effects to organs and the like).

However, due to the reactivity of HOCl or OCl— with oxidizable organicsubstances, its utility in wound care applications has previously beenlimited. For example, some prior art methods of generating hypochlorousacid have required electrolysis of saltwater or the like (e.g., withexpensive equipment at a patient's bedside). By way of another example,commercially available chemicals (e.g., bleach) have a hypochlorous acidconcentration of 5% or greater, which is too high to permit medical uses(e.g., will cause cytoxicity). Additionally, at suitable medicalconcentrations (e.g., 2-20 mM hypochlorous acid solutions),approximately 99% or more of the solution is water, such that shippingis more expensive and/or more difficult than necessary. Further, storageof hypochlorous acid solutions is difficult, as reactions withcontainers typically degrade or reduce the concentration of thesolution. However, the present wound inserts can be deposited withreactive agents (have reactive agents deposited in the foam of the woundinserts) such that upon application of a fluid such as saline or water,OCl (and/or ClO⁻) is released (e.g., to form hypochlorous acid) anddelivered to a wound for biocidal action.

In the present embodiments, the foam and reactive agents can be selectedsuch that the foam will not be degraded by the reactive agents (and/orproducts of the reactive agents and the fluid). The inventors of thepresent disclosure were surprised to discover the stability of thepresent silicone foams because testing with silicone tubes resulted indegradation of the hypochlorous acid and/or hypochlorite ion. However,the present silicone foams were compatible with the hypochlorous acidsolutions (e.g., 0.1% hypochlorous acid solution), as discussed in thisdisclosure. For example, FIG. 4 depicts a photograph of a silicone foam300 suitable for some embodiments of the present wound inserts, and FIG.5 depicts a photograph of silicone foam 300 deposited with particles 304of Ca(OCl)₂ salt. Foam 300 shown in FIG. 5 is an open-celled foam thatis inert and stable in the presence of the Ca(OCl)₂ salt particles 304such that foam 300 can be pre-deposited with the reactive agent, andshipped and/or stored without degradation of the reactive agent and/orwithout degradation of the foam; and such that foam 300 providesdistribution channels or manifolds to permit dispersion of generallynon-reactive fluids such as saline through foam 300 to dissolve and/orrelease the reactive agent (e.g., NaOCl salt, Ca(OCl)₂ salt, etc.) anddeliver the reactive agent, and/or a reaction product of the reactiveagent and fluid, to the wound. For example, in FIG. 5, the Ca(OCl)₂ saltparticles are shown encapsulated in a suspension agent comprisingpolycaprolactone (PCL). In some embodiments, the reactive agent and/orthe suspension agent are in dry and/or particle form. In otherembodiments, the reactive agent and/or the suspension agent can be in agel and/or droplet form. Examples of suitable silicone foams areavailable from Rogers Corporation, in Rogers, Conn., U.S.A. (certainproduct lines recently acquired from MTI Global, Inc., in Mississauga,Ontario, CANADA; and/or MTI Specialty Silicones, in Richmond, Va.,U.S.A.), including for example, foams marketed as MagniFoam MF1-6535,MagniFoam MF1-8055, and/or MagniFoam MF1-9575.

Embodiments of the present wound inserts can comprise any of a varietyof suitable reactive agents (e.g., dry and/or anhydrous reactiveagents). For example, in some embodiments, the reactive agent comprisesa hypochlorite salt (e.g., a dry and/or anhydrous hypochlorite salt),and/or is configured to react with water to form release hypochloriteion (e.g., a salt or the like, that when dissolved by a fluid, can reactor combine with the fluid to release hypochlorite ion and may also formhypochlorous acid, such as, for example, depending on pH). As used inthis disclosure, “dry” refers to the absence of free water molecules inthe salt used for the reactive agent (e.g., H₂O molecules may be presentin certain salt crystalline structures, but such H₂O molecules are notfree). In some embodiments, the hypochlorite salt used to make thepresent wound inserts may have a free water content of less than 2% byweight or less than 2% w/v. In some embodiments, the reactive agentcomprises a substance defined by M(OCl)n, where n=1 if M is K⁺(potassium), Na⁺ (sodium), or Li⁺ (lithium); and where n=2 if M is Ca²⁺(calcium) or Mg²⁺ (magnesium). In some embodiments, the reactive agentcomprises at least one of: an N-chloro taurine; an N,N-dichloro taurine;an N-halogenated amino acid; an N,N-dihalogenated amino acid; and/or acombination of any two or more of these. Some embodiments comprise(alternatively or additionally) an agent comprising a growth factor; aprotein; a peptide; or a combination thereof.

In some embodiments, the reactive agent can be deposited onto and/orinto the open-cell foam with a chemically compatible polymer suspensionor binding agent, such as, for example, to encapsulate the reactiveagent for controlled release, improve physical stability of the reactiveagent in the foam, and/or bind or adhere the reactive agent to the foam.For example, in some embodiments, the wound insert comprises asuspension agent that includes at least one of: a polyvinylpyrrolidone,a polyethylene oxide (PEO), a polyvinyl acetate (PVA), a polyvinylalcohol (PVOH), an ethylene vinyl alcohol (EVOH) copolymer, an ethylenestyrene copolymer, polycaprolactone (PCL), polysorbate, and/or acombination of any two or more of these. In some embodiments, thesuspension agent is configured to dissolve in the presence of a solvent.For example, the suspension agent can be water soluble. In someembodiments, the reactive agent is dispersed throughout at least aportion (up to all) of the foam (e.g., a volume of the foam). In someembodiments, the reactive agent is coupled to a side of the foam (e.g.,a bottom side adjacent to the wound when the wound insert is disposed onthe wound).

Embodiments of the present wound inserts can comprise any suitable foamthat is inert, chemically stable, and/or resistant to degradation in thepresence of the reactive agent (and/or a product of the reactive agent).For example, in some embodiments, the foam comprises a fluoropolymer(e.g., a fluoropolymer comprising at least one of:polytetrafluoroethylene (PTFE), polyvinylidene fluoride (PVDF),perfluoroalkoxy (PFA) polymer, fluorinated ethylene-propylene copolymer(FEP), and/or a combination of any two or more of these). In someembodiments, the foam comprises a polyolefin and/or a polyolefincopolymer, such as, for example, polyethylene vinyl acetate copolymer(EVA), polyethylene vinylalcohol copolymer (EVOH),polyethylene-propylene copolymer, polyethylene-hexene copolymer (e.g.,an olefin comprising at least one of: ethylene, propylene, butene,pentene, hexene, heptene, or a combination of any of these).

The present wound inserts (e.g., comprising a foam deposited with areactive agent) provides a relatively easy delivery system fordelivering or instilling highly effective (but often generally unstable)antimicrobial agents to the wound site at controlled rates for effectiveinfection prevention and/or control to expedite wound healing. Thepresent wound inserts (pre-deposited with reactive agents) can eliminatethe need for complex and/or expensive on-site solution generation (e.g.,electrolysis solutions such as are offered by PuriCore), and/or caneliminate the need for shipping or storing pre-mixed aqueousantimicrobial solutions (which generally contain more than 99% water);and/or enables the use of antimicrobial solutions (which may generallybe chemically unstable) with negative pressure wound therapy (NPWT),such as, for example, by mixing such solutions at the wound.

Referring now to FIGS. 6-13, several experiments were performed onvarious materials to develop data indicative of which materials would besuitable for foams, reactive agents, and suspension agents of thepresent wound inserts, and/or suitable for fluids for releasing and/ordelivering reactive agents to a wound. Hypochlorite typically has acharacteristic absorption wavelength at about 292 nm in the ultraviolet(UV) spectrum. As illustrated in certain of FIGS. 6-13, absorbance at292 nm was used to quantify the presence of hypochlorite OCl—. Tocapture the total active chlorine, pH of a solution generally should beadjusted to 8 or higher to convert all hypochlorous acid intohypochlorite.

FIG. 6A depicts a chart of ultraviolet (UV) spectra of aqueous solutionsof calcium hypochlorite Ca(OCl)₂ at various concentrations between 0 and5 milliMolar (mM—0.001 moles per liter). More particularly, curve 354corresponds to a solution having 0.56 mg of Ca(OCl)₂ per mL; curve 358corresponds to a solution having 0.16 mg of Ca(OCl)₂ per mL; curve 362corresponds to a solution having 0.032 mg of Ca(OCl)₂ per mL; and curve366 corresponds to a solution having 0.0064 mg of Ca(OCl)₂ per mL. Asillustrated, as the concentration of calcium hypochlorite in thesolutions decrease, the absorption at 292 nm (generally corresponding tothe concentration of hypochlorite OCl—) decreased.

FIG. 6B depicts a chart illustrating the correlation of hypochloriteconcentration from the UV absorbance of FIG. 6A with correspondingconcentrations obtained by Iodine titration. FIG. 6C depicts a chart ofOCl⁻ concentration in solutions with certain of the present suspensionagents, including a control of only Ca(OCl)₂ in solution (of methylenechloride), Ca(OCl)₂ in PCL-1 solution having 0.5 g of PCL per 100 mL ofmethylene chloride; Ca(OCl)₂ in PCL-2 solution having 1.0 g of PCL per100 mL of methylene chloride; and Ca(OCl)₂ in solution with TWEEN 80(also known as polysorbate 80) having 0.1 g of TWEEN 80 per 10 g ofmethylene chloride. As indicated, the suspension agents did notsubstantially react with or otherwise consume or degrade the OCl⁻. Foreach solution, approximately 13 mg of Ca(OCl)₂ was added to eachmethylene chloride solution and the solution was placed in the dark fora period of about one hour. Then 5 mL of distilled water was added toeach solution, and each was shaken to mix its respective ingredients.The PLC-1 and PLC-2 solutions were allowed to sit for approximately fiveminutes to permit the contents to settle and separate into a PLC layerand an aqueous layer. The TWEEN 80 solution was allowed to sit forapproximately two hours to permit the contents to settle and separateinto a TWEEN 80 layer and an aqueous layer. After settling, for eachsolution, one milliliter of the aqueous layer was removed and mixed with10 mL of 0.1 N NaOH (e.g., to increase the pH to ensure all hypochlorousacid is converted to hypochlorite for complete capture of activechlorine), and evaluated with UV-Vis spectroscopy to determine theconcentration of OCl (e.g., to determine whether the OCl— had degradedor been consumed by the polymer). The test results verify that PCL andTWEEN 80 are compatible with Ca(OCl)₂ such that PCL or TWEEN 80 can beused as a suspension agent the Ca(OCl)₂ salt (e.g., to encapsulate orsuspend the Ca(OCl)₂ salt).

Further details of certain examples of reactive agents and suspensionagents are listed in Table 1. The Luvitec® K materials (e.g. Luvitec®K30, Luvitec® K90, etc.) are polyvinylpyrrolidones commerciallyavailable as powder or solution from BASF Corporation, Florham Park,N.J., U.S.A. Luvitec® VA64M is a vinylpyrrolidone/vinylacetate copolymeravailable from BASF Corporation, Florham Park, N.J., U.S.A. Chemlock®607 is manufactured by LORD Corporation and is available from numerousdistributors through the U.S.A. KBE-903 refers to3-trimethoxysilylpropan-1-amine (CAS No. 86158-92-1; chemical formulaC₆H₁₇NO₃Si). CF1-141 is a silicone (silane) primer available fromnumerous distributors throughout the U.S.A. P5200 Adhesion Promotercomprises: octamethyltrisiloxane, 1-Methoxyisopropyl orthosilicate,Tetrapropyl orthosilicate, and Tetrabutyl titanate, and is availablefrom DOW Corning Corporation, Midland, Mich., U.S.A. 1205 Prime Coatcomprises: Propylene glycol methyl ether; Toluene; Butyl glycol acetate;Bisphenol A, p-tert-butylphenol, (chloromethyl)oxirane polymer; and2-Methoxypropanol; and is available from DOW Corning Corporation,Midland, Mich., U.S.A. 1200 RTV Prime Coat Clear comprises: Lightaliphatic petroleum solvent naphtha; Xylene; Tetrapropyl orthosilicate;Tetrabutyl titanate; Tetra (2-methoxyethoxy) silane; Ethylene glycolmethyl ether; and Ethylbenzene; and is available from DOW CorningCorporation, Midland, Mich., U.S.A.

TABLE 1 Examples of Suspension Agents, Properties, Applications, andSuppliers Binder Material Properties Application SupplierPoly(vinylalcohol) Mw 124,000-186,00 polymer AldrichPolyvinylpyrrolidone Mw 10,000 polymer, gel Aldrich Poly(ethylene oxide)Mw ~8,000,000 polymer Aldrich Poly(vinyl 44 mol % ethylene polymerAldrich alchohol-co-ethylene) KBE-903 3-Aminopropyltriethoxysilaneprimer ShinEtsu Luvitec K30 30% solution polymer, gel BASF Luvitec K9020% solution, Brookfield viscosity 10,000-40,000 mPa s polymer, gel BASFLuvitec VA64W Vinylpyrolidon Vinylacetate copolymer polymer, gel BASF1200 Clear RTV Prime Contains: naptha, tetrapropyl othosilicate,tetrabutyl primer DowCorning Coat titinate, ethylene glycol methylether, tetra(2-methoxyethoxy)silane, ethyl benzene 1205 Prime Coatpropylene glycol methyl ether, toluene, butylglycol primer DowCorningacetate, bisphenol A, p-tert-butylphenol, (chloromethyl)oxirane polymer,2-methoxypropanol P5200 Adhesion octamethyltrisilioxane, tetrabutyltitanate, primer DowCorning Promoter 1-methoxyisopropylorthosilicate,tetrapropylorthasilicate, n-butyl alcohol CF1-141 Silicon PrimerContains: IPA primer NuSil Chemlok 607 Contains: MeOH, EtOH primer LordChitosan Low Mw Brookfield viscosity 20,000 cps polymer Aldrich ChitosanMedium Mw Brookfield viscosity 200,000 cps polymer AldrichPoly(styrene-ran- 5% polymer solution in 1-propanol: styrene, 76 wt. %;gel Aldrich ethylene) sufonate sulfonated styrene units, 32-38%; vinylsilane crosslinking agent, <0.5% Polycaprolactone (PCL) Mx 14,000;45,000; or 80,000 pellets Aldrich

FIG. 7 depicts release profiles of silicone foam (rectangular pieces ofsilicone foam (measuring 4 inches×3 inches×1.25 inches) deposited withNaOCl salt. Curve 340 shows the molar increase in concentration of NaOClin 500 milliliters (mL) of saline solution corresponding to theaccumulated release of NaOCl salt from a saturated silicone foam over aperiod of 60 minutes; and curve 342 shows the corresponding rate ofrelease of NaOCl from the foam over the same 60-minute period.Additionally, curve 344 shows the molar increase in concentration ofNaOCl in 500 mL of saline solution corresponding to the accumulatedrelease of NaOCl salt from an unsaturated silicone foam over a period of60 minutes, and curve 346 shows the corresponding rate of release ofNaOCl in the unsaturated foam over the same 60-minute period.

FIG. 8 depicts a release profile of silicone foam (rectangular piece ofsilicone foam measuring 4 inches×3 inches×1.25 inches) deposited withPEO/NaOCl (particles of a reactive agent comprising NaOCl, encapsulatedin a suspension agent comprising polyethylene oxide (PEO)). Moreparticularly, curve 350 shows the molar increase in concentration ofNaOCl in 500 mL of saline solution, as measured by titration; and curve354 shows the molar increase in concentration of NaOCl in 500 mL ofsaline solution corresponding to the release of NaOCl from the foam, asmeasured by UV-visible (UV-Vis) spectroscopy; both over a period of 60minutes, as shown.

FIG. 9 depicts a release profile of PCL/Ca(OCl)₂ (Ca(OCl)₂ encapsulatedin PCL). More particularly, 7.2 g of the PCL-1 solution described abovewith reference to FIG. 6C was placed in the bottom of a 500 mL glassbeaker and allowed to dry overnight. Approximately 0.63 g ofPCL/Ca(OCl)₂ remained once the fluid evaporated. Approximately 300 mL ofsaline solution at pH=4 was added to the beaker, and mechanicallystirred to disperse the PCL/Ca(OCl)₂ in the saline. 1 mL aliquots werethan removed from the beaker (at various time intervals between 1 and1380 minutes), diluted with 10 mL of 0.1 NaOH (e.g., to increase the pHto ensure all hypochlorous acid is converted to hypochlorite forcomplete measurement by UV-V is spectroscopy), and evaluated with UV-Visspectroscopy to determine the molar concentration of hypochlorite ClO—,and the results plotted (FIG. 9) to approximate the release profile ofCa(OCl)₂ from the PCL suspension agent.

FIG. 10 depicts a release profile, of a silicone foam deposited withLuvitec® K90/NaOCl (particles of a reactive agent comprising NaOClencapsulated in a suspension agent comprising Luvitec® K90) released intwo liters (L) of saline solution. More particularly, FIG. 10 depictsthe release profile of the silicone foam (rectangular piece of siliconefoam measuring 4 inches×3 inches×1.25 inches) deposited with LuvitecK90/NaOCl (a reactive agent comprising NaOCl encapsulated in asuspension agent comprising Luvitec® K90). More particularly, curve 370shows the accumulated molar increase in concentration of NaOCl in 500 mLof saline solution, as measured by titration; and curve 374 shows theaccumulated molar increase in concentration of NaOCl in 500 mL of salinesolution corresponding to the release of NaOCl from the foam, asmeasured by UV-visible (UV-Vis) spectroscopy; both over a period of 60minutes, as shown.

FIG. 11 depicts a release profile of a silicone foam deposited with thePSES/NaOCl (a reactive agent comprising NaOCl encapsulated in asuspension agent comprising PSES) in two liters (L) of saline. Detailsfor the PSES are provided above in Table 1. More particularly, FIG. 11depicts the release profile from a rectangular piece of silicone foam(measuring 4 inches×3 inches×1.25 inches) deposited with the PSES/NaOCl.More particularly, curve 390 shows the molar increase in concentrationof NaOCl in 500 mL of saline solution, as measured by titration; andcurve 394 shows the molar increase in concentration of NaOCl in 500 mLof saline solution corresponding to the release of NaOCl from the foam,as measured by UV-visible (UV-Vis) spectroscopy; both over a period of60 minutes, as shown.

FIGS. 12A-12B depict charts of stability data for various foams soakedin hypochlorous acid solution. FIG. 12A illustrates HOCl concentrationover time relative to initial HOCl concentration in a solution(initially 10 mM HOCl solution) passed through silicone foam (curve 396)and passed through polyurethane foam (curve 398) using a wound treatmentsystem such as a VAC Instill device available from KCI. As shown, thepolyurethane foam reacted with the HOCl to reduce the HOCl concentrationin the solution, while the silicone foam was relatively stable such thatthe HOCl concentration remained relatively constant over the 12-minutetest period. For FIG. 12B, various foams were soaked in 0.1%hypochlorous acid (HOCl) solutions for 12 minutes. Curves 400-410 showconcentration of HOCl (e.g., fluctuations in concentration due toreaction with the foam) for several foams, such that the greater thereduction in concentration, the less stable the foam. Curve 400 showsthe concentration over time for a polyurethane foam; curve 402 shows theconcentration over time for MF1-6535, a silicone foam; curve 404 showsthe concentration over time for MF1-8055, a silicone foam; curve 406shows the concentration over time for MF1-9575, a silicone foam; andcurve 408 shows the concentration over time for Virgin HOCl in a glassbottle for control (baseline and comparison) purposes. As shown, thepolyurethane foam degraded in the hypochlorous acid solution, while thesilicone foams were relatively stable.

FIGS. 13A-13E depict photographs illustrating tests performed on variousfoams to determine stability or physical integrity of the foams inhypochlorous acid solution. FIG. 13A depicts an experimental apparatus450 used to evaluate stability or physical integrity of each of thefoams evaluated for FIG. 11 through a number of cycles over a period offive days. Apparatus 450 is similar to the wound dressing 18 shown inFIGS. 1 and 3B, in that apparatus 450 includes a foam wound insert 454covered by a drape 38, and in communication with a fluid source viaconnection pad 54 a, and in communication with a vacuum source viaconnection pad 54 b. An apparatus 450 was configured for the PU foam,and each of the silicone foams referenced above for FIG. 12B. The fluidsource and vacuum sources were each sequentially activated repeatedlyover a five-day period for each of the foams to deliver and remove a0.1% hypochlorous acid solution to each of the foams. As shown in FIGS.13B-13D, the silicone foams remained stable for the exposure. As shownin FIG. 13E, polyurethane foam collapsed and disintegrated as a resultof oxidation.

FIG. 14 depicts a chart of hypochlorite concentration at various timesover multiple cycles of saline solution through one of the present woundinserts. For the chart shown, a suspension (or binding) agent, PCL (Mw80,000), was mixed with Dichloromethane (DCM or methylene chloride) toform a 10% w/v PCL/DCM solution. Ca(OCl)₂ was then mixed into thePCL/DCM solution to form a slurry (Ca(OCl)₂ is generally not soluble inDCM). An oval-shaped piece of silicone foam having a volume of 12.05cubic inches (in³) was then placed in the PCL/DCM/Ca(OCl)₂ slurry andthe foam alternately compressed and relaxed to draw the slurry into thefoam, which resulted in a dispersion or loading of 0.63 grams of Calciumhypochlorite salt in the foam. Once the foam was substantiallysaturated, the foam was allowed to dry such that the DCM substantiallyevaporated from the foam to leave PCL-suspended (and/orPCL-encapsulated) Ca(OCl)₂ dispersed and deposited in the foam. Thewound insert was then placed in an experimental apparatus 450 (FIG.13A), and the experimental apparatus 450 was coupled to a VAC-Instilldevice commercially available from KCI for delivery/removal of fluidsto/from the wound insert in the experimental apparatus. Normal salinesolution (0.9% NaCl) was then delivered to the wound insert and thewound insert allowed to soak in the saline solution (e.g., to allow thesaline solution to dissolve a portion of the Ca(OCl)₂ reactive agent torelease hypochlorite ion in experimental apparatus 450. Each cycleincluded: activating a pump for 40 seconds to deliver the salinesolution to the wound insert, allowing the wound insert to soak in thesaline solution for 14 minutes, measuring the concentration ofhypochlorite in the experimental apparatus 450 at various periods duringthe 14-minute soak period, and activating a vacuum source for 5 minutesto draw at least a portion the fluid out of the wound insert. Thissequence was repeated 5 times (5 cycles). The hypochloriteconcentrations for each cycle are shown in FIG. 14, with thehypochlorite concentration at 6 minutes into the soak period shown bythe left bar, and the hypochlorite concentration at 12 minutes into thesoak period shown by the right bar. As is shown, the hypochloriteconcentration increases with soaking time, but decreases over multiplecycles. The suspension (or binding) agent (e.g., PCL) can be configuredto permit the controlled release of an effective (e.g., antimocrobiallyeffective) dose of the reactive agent, while still permittingsubstantially all of the reactive agent to be flushed from the woundinsert over multiple cycles, thus reducing potential for long-termtissue damage that may otherwise result from the sustained orun-dissipating presence of reactive agents.

FIG. 15 depicts a flowchart conceptually illustrating an embodiment 500of the present methods of manufacturing the wound insert tested toobtain the data of FIG. 14. In the embodiment, shown, the methodcomprises a step 504 of adding dry hypochlorite salt particles to asolution containing dissolved binding and/or encapsulating agent (e.g.,polymer) such that the solution and hypochlorite salt form a slurry.Calcium hypochlorite (and other hypochlorite) salts are commerciallyavailable from a variety of sources. For example, Calcium hypochloriteis available from Sigma-Aldrich, PPG Industries, and Arch Chemicals,Inc. Such Calcium hypochlorite salts are also available with a range ofavailable Chlorine contents (e.g., 34%-76%). In some embodiments, thehypochlorite salt has an available Chlorine content of 50% or more(e.g., at least 60%, at least 70%, or more). Other examples ofhypochlorite salts are defined by M(OCl)n, where n=1 if M is K⁺, Li⁺, orNa⁺, and where n=2 if M is Mg²⁺.

In some embodiments, the solution comprises a polymer (binding agentand/or encapsulating agent) and a liquid that is a solvent of thepolymer but not a solvent of the hypochlorite salt. For example, in theembodiment shown, the polymer is PCL. In other embodiments, the polymercan be another suitable biocompatible (e.g., biodegradable) polymer thatis not water-soluble. For example, in the embodiment shown, the liquidis non-aqueous and comprises Dichloromethane (DCM or methylenechloride). In other embodiments, the liquid comprises a differentnon-aqueous solvent of the polymer (e.g., Tetrahydrofuran (THF) orCyclohexane for PCL). The concentration of polymer in the liquid can be,for example, between 5% w/v and 10% w/v. For example, a concentration of7% w/v (which may in some embodiments be between 6% and 8%) has workedwell for certain experiments described below. In the embodiment shown,method 500 further comprises a step 508 of substantially removing theliquid from the slurry such that at least a portion of the hypochloritesalt particles are at least partially encapsulated by the polymer. Forexample, removing the liquid may be performed by drying (e.g., in vacuumand/or at ambient pressure). In the embodiment shown, all references to“solvent” are to DCM, which is also noted as a “Non-solvent” at step 504because DCM is not a solvent for Ca(OCl)2 (e.g., Calcium Hypochlorite isgenerally not soluble in DCM).

In some embodiments, method 500 comprises a step 512 of forming thesolution by combining the liquid and the polymer (to dissolve thepolymer in the liquid). In some embodiments, method 500 comprises a step516 of reducing, prior to adding the hypochlorite salt particles intothe solution, the size of the hypochlorite salt particles such that amajority of the hypochlorite salt particles have a size at or below atarget size. For example, for certain silicone foams discussed in thisdisclosure, the pore size is such that a target size of 180 micronspermits adequate dispersion of the salt particles through the foam. Forexample, in some embodiments of commercially available Ca(OCl)₂, theaverage particle or aggregate size is approximately 1 millimeter (MM),and average particle size is reduced by disposing hypochlorite particles(e.g., pellets) into a slurry with Dichloromethane (DCM or methylenechloride) and shearing with a high-shear mixer (e.g., at 7000 rpm for 5minutes, 7000 rpm for 7 minutes, 10000 rpm for 7 minutes, and/or otherspeeds or durations) to break larger particles into smaller particles.Particle size (e.g., the target size for a group of particles) may beadjusted for various applications of the present embodiments. Forexample, in a wound insert with hypochlorite salt at least partiallyencapsulated by PCL, larger salt particles will generally dissolve moreslowly than smaller salt particles, and vice versa. In the embodimentshown, the solvent (DCM) is removed from the salt (or the salt isremoved from the solvent) after reducing the particle size (e.g., may befiltered, evaporated, and/or otherwise recovered prior to introducingthe hypochlorite salt particles into the solution).

In some embodiments, method 500 comprises a step 520 of disposing a foamwound insert in the slurry such that hypochlorite sale particles andpolymer are dispersed within the wound insert, prior to step 508 ofsubstantially removing the liquid. For example, the foam may becompressed and released one or more times in the presence of the slurrysuch that expansion of the foam will draw the slurry into the pores ofthe foam. The foam may be any suitable open-celled foam that is stable(will not degrade) in the presence of hypochlorite ion or hypochlorousacid (e.g., at least at concentrations present in the discussedembodiments). Examples of suitable foams include Silicone foams having adensity in the range of 25-150 kg/m³ (e.g., MagniFoam 6535, MagniFoam8055, and MagniFoam 9575, manufactured by Rogers Corporation), Polyvinylalcohol (PVOH), and the like.

In some embodiments, step 520 may be accomplished with the apparatus 524of FIG. 16. Apparatus 524 includes a body 528 defining a chamber 532sized to receive a piece of foam to be used for a wound insert. Thepolymer/solvent/salt slurry and the foam can be disposed in chamber 532,and the foam compressed and permitted to expand to draw the slurry intothe pores of the foam (e.g., can be sequentially compressed and allowedto expand multiple times). In some embodiments, the foam is compressedin the chamber with a plunger (not shown) having openings therethrough(and/or corresponding in shape to the chamber). Chamber 532 can be sizedto correspond to a single wound insert, can be sized to correspond to alarger piece of foam from which multiple wound inserts can be cut afterbeing infused with the slurry. Other embodiments may include multiplecavities each corresponding to a single wound insert. For example, thedata shown in FIG. 14 was obtained with a mold having cavity dimensionsof l=4.5 inches×w=3.5 inches×h=2 inches. Although not shown in FIG. 16for simplicity, the inside corners of cavity 532 were also filleted(rounded) on radiuses of 0.5 inches. For other sizes of individual woundinserts, the cavity may be provided with any suitable dimensions (e.g.,l=3.5 inches×w=3.5 inches×h=2 inches).

In some embodiments, the slurry is dispersed into the foam such thatonce the solvent is removed and the foam dried, the hypochlorite saltconcentration in the foam is between 0.03 and 0.2 grams per cubic inch(g/in³). For example, to generate the data of FIGS. 14 and 17, a4-inch×3-inch×1.25-inch oval-shaped piece of foam was used having avolume of 12.05 cubic inches (in³), and between 0.5 and 2.0 grams ofCalcium hypochlorite salt were infused into the foam for variousiterations. The concentration of hypochlorite per cubic inch of foam canbe increased or decreased to vary the release profile of hypochloriteion from the foam, and may vary for different foams and/or polymers(binding/encapsulating agents).

Referring now to FIG. 17, the experiments described above for FIG. 14were also performed with additional foams, one foam in which 1 gram ofCalcium hypochlorite salt was infused (D100, shown as left column foreach cycle), and one foam in which 2 grams of Calcium hypochlorite saltwas dispersed (D200, shown as right column for each cycle). As shown inFIG. 17, a single foam wound insert released enough hypochlorite ion tocause the liquid to have a concentration of hypochlorite ion in each oftwelve sequential cycles between 0.5 and 18 mM. As discussedadditionally below, the minimum concentration is significant becausetesting identified concentrations of hypochlorite-ion as low as 0.5-0.7mM to have effective antibacterial and antimicrobial properties.Additional testing was performed to measure the zone of inhibition (ZOI)and Log Reduction of microbes for various samples of released aqueoussolutions having various concentrations of hypochlorite ion, as listedin Tables 2 and 3. Table 2 lists ZOI and Log reduction data for a singlecycle measured at hold times (exposure duration) of 30 seconds and 5minutes of bacterial exposure to solution. Table 3 lists ZOI and Logreduction data for multiple cycles (each cycle including introduction ofhypochlorite solution, and removal of solution prior to beginning nextcycle). In the ZOI experimentation, foam discs having a diameter of 8millimeters (mm) and a height of 5 mm were each saturated withhypochlorite-ion solution as indicated. Table 3 also lists the initialmicrobe count in log form (10^(X), where X is listed in Table 2), logreduction in microbe count, and ZOI in mm. For the data of Table 3, theinitial concentration (1×) of hypochlorite ion in solution was 5.7 mM ofhypochlorite ion, which corresponds to 0.041% w/v of Ca(OCl)². In theLog reduction experimentation, the microbes were exposed to therespective concentration of solution for 30 seconds per cycle. It wasobserved that five (5) cycle sat even the lowest concentration (0.7 mM)killed substantially all microbes present. The bold entries in Table 3are indicative of substantially all microbes being killed. In thebiofilm eradication cycles listed in Table 6 below, probes were culturedwith microbes and incubated to permit formation of a biofilm on theprobe. The probe was then exposed to solutions having variousconcentrations of Calcium hypochlorite solution for multiple cycles,with each cycle including exposure of the probe to solution for aduration of 5 minutes.

TABLE 2 ZOI and Log Reduction Data for OCl⁻ Solutions HOCl/OCl− ΔLog -MRSA ΔLog - C. alb. ZOI, D in mm mM 30 sec. 5 min. 30 sec. 5 min. MRSAC. alb. 15.7 >6.93 >7.13 3.50 >7.18 13.0 44.3 10.7 >6.93 >7.137.18 >7.18 13.0 45.7 4.0 5.52 >7.13 3.94 >7.18 0.0 34.3 3.1 3.55 >7.133.08 >7.18 0.0 22.0 1.9 2.93 4.09 2.94 3.77 0.0 24.3 0.8 2.96 2.992.87 >7.18 0.0 15.0 Microbe Count 7.93 8.13 8.18 8.18 — —

TABLE 3 ZOI and Log Reduction Data for OCl⁻ Solutions Pseudomonasaeruginosa Staphylococcus aureus Staphylococcus aureus Sample ATCC 27853ATCC 10832 USA 400 (MRSA) Dilution 1 Cycle 3 Cycles 5 Cycles 1 Cycle 3Cycles 5 Cycles 1 Cycle 3 Cycles 5 Cycles 1x −0.16 5.87 5.83 3.21 2.822.66 4.15 3.63 3.91 2x −0.98 5.87 5.83 3.21 2.82 2.66 4.15 3.63 3.91 4x−0.48 3.92 5.83 3.21 2.82 2.66 4.15 3.63 3.91 8x −1.11 1.26 5.39 3.212.82 2.66 4.15 3.63 3.91

As illustrated by the data in Table 2 and Table 3, the minimuminhibitory concentration (MIC), minimum bactericidal concentration(MBC), and minimum biofilm eradication concentration (MBEC) ofhypochlorite ion in solution (e.g., the solution formed by the releaseof hypochlorite ion when aqueous solution is added to the impregnatedfoam) for each of Pseudomonas aeruginosa ATCC 27853, Staphylococcusaureus ATCC 10832, and Staphylococcus aureus USA 400 (MRSA), at each of1 3, and 5 cycles, are listed in Tables 4, 5, and 6. 0.0051% w/vCa(OCl)₂ in water corresponds to 0.7 mM hypochlorite ion in water

TABLE 4 Minimum Inhibitory Concentration (MIC) (% w/v) Bacteria 1 Cycle3 Cycles 5 Cycles Pseudomonas aeruginosa <0.005% <0.005% <0.005% ATCC27853 Staphylococcus aureus ATCC 10832 <0.005% <0.005% <0.005%Staphylococcus aureus <0.005% <0.005% <0.005% USA 400 (MRSA)

TABLE 5 Minimum Bactericidal Concentration (MBC) (% w/v) Bacteria 1Cycle 3 Cycles 5 Cycles Pseudomonas aeruginosa <0.005% <0.005% <0.005%ATCC 27853 Staphylococcus aureus ATCC 10832 <0.005% <0.005% <0.005%Staphylococcus aureus <0.005% <0.005% <0.005% USA 400 (MRSA)

TABLE 6 Minimum Biofilm Eradication Concentration (MBEC) (% w/v)Bacteria 1 Cycle 3 Cycles 5 Cycles Pseudomonas aeruginosa >0.041% 0.021%0.041% ATCC 27853 Staphylococcus aureus ATCC 10832 <0.005% <0.005%<0.005% Staphylococcus aureus <0.005% <0.005% <0.005% USA 400 (MRSA)

In alternate embodiments (not shown), the polymer (PCL)/salt (Ca(OCl)₂)slurry can be formed into or added to alternate delivery structures(e.g., instead of dispersion in foam). For example, the liquid (e.g.,Dichloromethane) can be partially removed, and the slurry can beextruded or otherwise formed (e.g., cast) into sheets or fibers withencapsulated hypochlorite salt that can be reacted with water to releasehypochlorite ion and/or hypochlorous acid. Such sheets can be sized tobe used for wound dressings, and used as wound dressings (e.g., in thesystems and methods similar to those described above). Such fibers canbe woven into mats or sheets that can be used as wound dressings (e.g.,in the systems and methods similar to those described above). In otherembodiments, the slurry can be deposited on substrates other than foams.For example, the slurry can be sprayed or “printed” (e.g., using knownspraying or printing devices) onto wound dressings or other medicaldevices (e.g., onto a side of drape 38 that is configured to face awound).

FIG. 18 depicts an alternate embodiment of one of the present woundinserts 34 a that comprises an inert foam layer 600 that is depositedwith a reactive agent (e.g., comprising any of the materials and/orcomponents such as a suspension agent, as described above for woundinsert 34); and a second open-celled foam layer 604 that is coupled tothe first layer 600, and is not coupled to (not deposited with) thereactive agent. In accordance with the description above for the woundinsert 34, the first open-celled foam 600 is configured to be inert inthe presence of the reactive agent. Additionally, in the embodimentshown, foam 600 forms a first layer of wound insert 34 a, and foam 604forms a second layer of wound insert 34 a.

Referring now to FIG. 19, a cross-sectional side view of an apparatus700 is shown for making some embodiments of the present wound inserts(e.g., wound insert 34). Apparatus 700 comprises a housing 704, a lowerfilter 708, a reservoir region 712, a foam region 716, an upper filter720, and a vacuum manifold 724. Filters 708, 712 are coupled to housing704, and are configured to permit air to pass through filters 708, 712,and to prevent particles of reactive agent from passing through filters708, 712. Reservoir region 712 is configured to receive and/or be filledwith particles (e.g., a predetermined amount or volume of particles orpowder) of any of the reactive agents and/or suspension agents discussedin this disclosure. Foam region 716 is configured to receive a piece 618of any of the foams discussed in this disclosure (e.g., a silicone orother inert foam). Once a reactive agent (and/or suspension agent) isdisposed in reservoir region 712, a foam 718 is disposed in foam region716, top filter 720 can be coupled to housing 704 to substantiallyenclose reservoir region 712 and foam region 716. Some embodiments ofthe present methods of forming a wound insert comprise: applyingnegative pressure (e.g., via vacuum manifold 714) to an open-celled foam(e.g., 718) to draw particles (e.g., of a reactive agent) into the foamsuch that the particles become dispersed throughout at least a portionof the foam.

In the embodiment shown, foam 718 has a first side (adjacent top filter720) and a second side (adjacent reservoir region 712), and someembodiments of the present methods further comprise: disposing the foambetween a filter (e.g., top filter 720) and a particle reservoir (e.g.,reservoir region 712), where top filter 720 is configured tosubstantially prevent passage of the particles (of reactive agent and/orsuspension agent) through top filter 720. In such embodiments, applyingnegative pressure can comprise: applying negative pressure to the filter(top filter 720) such that the particles (of reactive agent and/orsuspension agent) are drawn from the reservoir (reservoir region 712)into the foam (e.g., 718) but are prevented from passing through thefilter (top filter 720). In addition to the reactive agents describedabove, in some embodiments of the present methods of forming a woundinsert, the particles comprise a metal (e.g., silver) such that thesilver particles are drawn into the foam. These methods of forming thepresent wound inserts permit loading, dispersion, and/or deposition ofreactive agents in foam without soaking the foam in a liquid solutionand drying the foam to leave the solid agent in the foam. In contrast toprior methods, the present methods of vacuum loading is more efficientand can directly “charge” the foam with solid particles (e.g., powder).In some embodiments, the present wound inserts are configured to bedisposed with the bottom side (side adjacent reservoir region 612)adjacent a wound, such that as fluid is introduced it will direct theparticles in an opposite direction from the direction in which they weredrawn into the foam.

In some embodiments of the present wound inserts, rather than dispersinga dry reactive agent in a foam, the foam is packaged in a wet state inwhich the foam contains a liquid containing a reactive agent. Forexample, WhiteFoam is a polyvinyl alcohol (PVOH) open-celled foam woundinsert, currently available from KCI U.S.A., Inc., which is typicallypacked when the foam contains water in a moisture-barrier foil pouch toprevent evaporation of the water. In some embodiments, the present woundinserts comprise foam containing a liquid solution comprisingantimicrobial agents (e.g., polyhexanide). In some embodiments, thepresent wound inserts comprise a container enclosing the wound insertand configured to prevent evaporation of the solution from the woundinsert.

Referring now to FIG. 20, an exploded perspective view is shown ofanother embodiment 34 b of the present wound inserts. In the embodimentshown, wound insert 34 b comprises an open-celled foam 750 configured tobe disposed between a wound (e.g., 26) of a patient (e.g., 30) and adrape (e.g., 38) coupled to skin (e.g., 46) of the patient such that thedrape forms a space (e.g., 50) between the wound and the drape. Foam 750has an upper side 754 and a lower side 758 that is configured to facethe wound. In the embodiment shown, foam 750 comprises a plurality ofparticles A dispersed within foam 750, and a second metal B coupled to(e.g., coated on) lower side 758 of the foam. Additionally, foam 750 isconfigured such that a fluid can be introduced to generate microcurrentsbetween first metal A and second metal B (e.g., such that uponintroduction of fluid to the foam, microcurrents are generated betweenmetal A and metal B). Additionally, in the embodiment shown, particlesof first metal A are dispersed in foam 750 such that if a fluid passesthrough the foam at least some portion of first metal A will exit thefoam. In some embodiments, first metal A and first metal B compriseanode and cathode materials. For example, in some embodiments, metal Acomprises an anode metal and metal B comprises a cathode metal. By wayof another example, in some embodiments, metal A comprises a cathodemetal, and metal B comprises an anode metal. In some embodiments, firstmetal A comprises silver. In some embodiments, second metal B compriseszinc.

In the embodiment shown, wound insert 34 b further comprises: apermeable layer (e.g., mesh) 762 coupled to lower side 758 of foam 750;where second metal B is coupled to permeable layer 762. Additionally, inthe embodiment shown, wound insert 34 b is configured such that if afluid (e.g., water, saline, etc.) is passed through foam 750 from upperside 754 through lower side 758, at least some portion of first metal Awill exit foam 750 through lower side 758 and pass through permeablelayer 762 (e.g., to pass to a wound surface 42). For example, woundinsert 34 b is configured such that if wound insert 34 b is disposedsuch that permeable layer 762 is in contact with a wound 26 (e.g., awound surface 42) and a fluid is passed through foam 750 from upper side754 to lower side 758, at least some portion of first metal A will exitthe foam through permeable layer 762 and microcurrents will be generatedbetween first metal A and second metal B coupled to permeable layer 762.

Wound insert 34 b can thus be configured and/or used to providemicrocurrents to a wound, such as, for example, to stimulate activitiesof extracellular matrix (ECM), growth factors, cells, and tissues toenhance tissue regeneration and wound healing process. Additionally,such microcurrents can make microorganisms and associated biofilms moresusceptible to attack and destruction by a patient's immune systemand/or antibiotics or antiseptics. For example, first metal A(especially free metal A that travels to a wound surface) and secondmetal B can act as electrodes (e.g., for ΔV ˜1 volt) to generatemicrocurrents within the wound bed.

The various illustrative embodiments of devices, systems, and methodsdescribed herein are not intended to be limited to the particular formsdisclosed. Rather, they include all modifications and alternativesfalling within the scope of the claims. The claims are not intended toinclude, and should not be interpreted to include, means-plus- orstep-plus-function limitations, unless such a limitation is explicitlyrecited in a given claim using the phrase(s) “means for” or “step for,”respectively.

It will be understood that the benefits and advantages described abovemay relate to one embodiment or may relate to several embodiments. Itwill further be understood that reference to ‘an’ item refers to one ormore of those items, unless otherwise specified. The steps of themethods described herein may be carried out in any suitable order, orsimultaneously where appropriate.

Where appropriate, aspects of any of the examples described above may becombined with aspects of any of the other examples described to formfurther examples having comparable or different properties andaddressing the same or different problems. It will be understood thatthe above description of embodiments is given by way of example only andthat various modifications may be made by those skilled in the art. Theabove specification, examples and data provide a complete description ofthe structure and use of exemplary embodiments. Although variousembodiments have been described above with a certain degree ofparticularity, or with reference to one or more individual embodiments,those skilled in the art could make numerous alterations to thedisclosed embodiments without departing from the scope of thisinvention.

1. A wound insert, comprising: an open-celled foam configured to bedisposed between a wound of a patient and a drape coupled to skinadjacent the wound; and a reactive agent disposed within the foam, andconfigured to be inert in the absence of an activating fluid and toexhibit antimicrobial properties in the presence of an activating fluid;where the reactive agent is configured to react with water to releasehypochlorite ion and/or form hypochlorous acid.
 2. The wound insert ofclaim 1, where the reactive agent comprises a hypochlorite salt definedby M(OCl) n, where n=1 if M is K⁺, Li⁺, or Na⁺, and where n=2 if M isCa²⁺ or Mg²⁺.
 3. The wound insert of claim 1, further comprising abiocompatible suspension agent that couples the reactive agent to thefoam and optionally at least partially encapsulates the reactive agent.4. The wound insert of claim 3, where the suspension agent comprisespolycaprolactone (PCL).
 5. The wound insert of claim 3, where the woundinsert is configured to release a hypochlorite ion in the presence of avolume of activating liquid such that after release the volume ofactivating liquid will have a concentration of hypochlorite ion between0.7 and 20 millimolar (mM).
 6. The wound insert of claim 5, where thewound insert is configured to release a hypochlorite ion in the presenceof each of three or more sequential volumes of activating liquid suchthat after release each sequential volume of activating liquid will havea concentration of hypochlorite ion between 0.7 and 20 millimolar (mM).7. The wound insert of claim 3, where the foam comprises silicone. 8.The wound insert of claim 3, further comprising: a second open-celledfoam that is not coupled to the reactive agent; where the firstopen-celled foam is configured to be inert in the present of thereactive agent, and forms a first layer of the wound insert; and wherethe second open-celled foam forms a second layer of the wound insert,and is coupled to the first open-celled foam.
 9. A wound dressingcomprising: a wound insert of claim 3; a drape configured to be coupledto skin adjacent a wound of a patient.
 10. A wound-treatment apparatuscomprising: a wound dressing of claim 9; a fluid source configured to becoupled to the wound dressing such that the fluid source is actuatableto deliver a fluid to the wound dressing.
 11. The apparatus of claim 10,further comprising: a vacuum source configured to be coupled to thewound dressing such that the vacuum source is actuatable to applynegative pressure to the wound dressing.
 12. A method comprising: addinghypochlorite salt particles to a solution such that the solution andhypochlorite salt form a slurry, the solution comprising a polymer and aliquid that is a solvent of the polymer but not a solvent of thehypochlorite salt; substantially removing the liquid from the slurrysuch that at least a portion of the hypochlorite salt particles are atleast partially encapsulated by the polymer.
 13. The method of claim 12,where the hypochlorite salt is defined by M(OCl) n, where n=1 if M isK⁺, Li⁺, or Na⁺, and where n=2 if M is Ca²⁺ or Mg²⁺.
 14. The method ofclaim 13, where the hypochlorite salt is defined by Ca(OCl)².
 15. Themethod of claim 12, where the polymer is biocompatible and optionallybiodegradable.
 16. The method of claim 15, where the polymer is notwater soluble.
 17. The method of claim 16, where the polymer comprisespolycaprolactone (PCL).
 18. The method of claim 13, where the solvent isnon-aqueous.
 19. The method of claim 18, where the solvent comprises atleast one of Dichloromethane (DCM or methylene chloride),Tetrahydrofuran (THF), or Cyclohexane.
 20. The method of claim 12,further comprising: disposing, prior to substantially removing theliquid, a foam in the slurry such that hypochlorite sale particles andpolymer are dispersed within the foam.
 21. The method of claim 20,further comprising: reducing, prior to adding the hypochlorite saltparticles into the solution, the size of the hypochlorite salt particlessuch that a majority of the hypochlorite salt particles have a size ator below a target size.
 22. The method of claim 21, where the targetsize is 180 microns.